Ligation of Centrocyte/Centroblast Marker 1 on Epstein-Barr Virus-Transformed B Lymphocytes Induces Cell Death in a Reactive Oxygen Species-Dependent Manner

Yeong Seok Kim, Ga Bin Park, Young Mi Choi, Oh Suk Kwon, Hyun Keun Song, Jae Seung Kang, Young In Kim Hoehamer, Wang Jae Lee, Dae Young Hur

Research output: Contribution to journalArticle

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Abstract

After primary infection of B cells with Epstein-Barr virus (EBV), infected B cells express several viral homologs of human genes that promote activation (LMP1 and CD40) or survival (BHRF and BCL2). EBV-infected B cells also express germinal center phenotype markers, such as CD77, PNA, CD95, and CD38. This transformation of B cells by EBV infection resembles normal B-cell activation and differentiation arising in the germinal center. In the present study, we found that EBV-transformed B cells expressed centrocyte/centroblast marker 1 (CM1), a possible marker of GC B cells and an inducer of their apoptosis. Moreover, ligation of CM1 on EBV-transformed B cells by immobilized anti-CM1 monoclonal antibody induced cell death. The ligation of CM1 immediately increased the generation of intracellular reactive oxygen species (ROS) and disrupted the mitochondrial membrane potential. Pretreatment with N-acetyl cystein (an ROS inhibitor) almost completely blocked this cell death, but Z-VAD-fmk (a caspase inhibitor) did not. We further investigated whether apoptosis-inducing factor (AIF) and endonuclease G (EndoG), which are both related to caspase-independent cell death, would be translocated to the nucleus during the ligation of CM1. We found that AIF and EndoG were released to the cytosplam but not translocated to the nucleus. Moreover, cytochalasin D, a cytoskeleton disruptor, rescued the cells from CM1-mediated cell death and blocked ROS generation. Therefore, it is conceivable that CM1 signaling might provoke cytoskeleton polymerization and trigger ROS generation. Taking these observations together, we conclude that the ligation of CM1 on EBV-transformed B cells can cause cell death via the ROS produced by F-actin polymerization in a caspase-independent manner, although this cell death might be unrelated to AIF and EndoG release from the mitochondria.

Original languageEnglish (US)
Pages (from-to)795-807
Number of pages13
JournalHuman Immunology
Volume67
Issue number10
DOIs
StatePublished - Oct 1 2006

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Human Herpesvirus 4
Ligation
Reactive Oxygen Species
B-Lymphocytes
Cell Death
Apoptosis Inducing Factor
Germinal Center
Caspases
Cytoskeleton
Polymerization
Cytochalasin D
Epstein-Barr Virus Infections
Caspase Inhibitors
Mitochondrial Membrane Potential
Transcriptional Activation
Actins
Cell Differentiation
Cause of Death
Mitochondria
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy

Cite this

Ligation of Centrocyte/Centroblast Marker 1 on Epstein-Barr Virus-Transformed B Lymphocytes Induces Cell Death in a Reactive Oxygen Species-Dependent Manner. / Kim, Yeong Seok; Park, Ga Bin; Choi, Young Mi; Kwon, Oh Suk; Song, Hyun Keun; Kang, Jae Seung; Kim Hoehamer, Young In; Lee, Wang Jae; Hur, Dae Young.

In: Human Immunology, Vol. 67, No. 10, 01.10.2006, p. 795-807.

Research output: Contribution to journalArticle

Kim, Yeong Seok ; Park, Ga Bin ; Choi, Young Mi ; Kwon, Oh Suk ; Song, Hyun Keun ; Kang, Jae Seung ; Kim Hoehamer, Young In ; Lee, Wang Jae ; Hur, Dae Young. / Ligation of Centrocyte/Centroblast Marker 1 on Epstein-Barr Virus-Transformed B Lymphocytes Induces Cell Death in a Reactive Oxygen Species-Dependent Manner. In: Human Immunology. 2006 ; Vol. 67, No. 10. pp. 795-807.
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abstract = "After primary infection of B cells with Epstein-Barr virus (EBV), infected B cells express several viral homologs of human genes that promote activation (LMP1 and CD40) or survival (BHRF and BCL2). EBV-infected B cells also express germinal center phenotype markers, such as CD77, PNA, CD95, and CD38. This transformation of B cells by EBV infection resembles normal B-cell activation and differentiation arising in the germinal center. In the present study, we found that EBV-transformed B cells expressed centrocyte/centroblast marker 1 (CM1), a possible marker of GC B cells and an inducer of their apoptosis. Moreover, ligation of CM1 on EBV-transformed B cells by immobilized anti-CM1 monoclonal antibody induced cell death. The ligation of CM1 immediately increased the generation of intracellular reactive oxygen species (ROS) and disrupted the mitochondrial membrane potential. Pretreatment with N-acetyl cystein (an ROS inhibitor) almost completely blocked this cell death, but Z-VAD-fmk (a caspase inhibitor) did not. We further investigated whether apoptosis-inducing factor (AIF) and endonuclease G (EndoG), which are both related to caspase-independent cell death, would be translocated to the nucleus during the ligation of CM1. We found that AIF and EndoG were released to the cytosplam but not translocated to the nucleus. Moreover, cytochalasin D, a cytoskeleton disruptor, rescued the cells from CM1-mediated cell death and blocked ROS generation. Therefore, it is conceivable that CM1 signaling might provoke cytoskeleton polymerization and trigger ROS generation. Taking these observations together, we conclude that the ligation of CM1 on EBV-transformed B cells can cause cell death via the ROS produced by F-actin polymerization in a caspase-independent manner, although this cell death might be unrelated to AIF and EndoG release from the mitochondria.",
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AU - Kim, Yeong Seok

AU - Park, Ga Bin

AU - Choi, Young Mi

AU - Kwon, Oh Suk

AU - Song, Hyun Keun

AU - Kang, Jae Seung

AU - Kim Hoehamer, Young In

AU - Lee, Wang Jae

AU - Hur, Dae Young

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